Hepatic Damage Caused by Chronic Arsenic Toxicity in Experimental Animals

作者：Amal Kumar Santra, Amitabha Maiti, Subhankar Das, Sarbari Lahiri, Sushil K. Charkaborty, Debendra N. Guha Mazumder, Debendra Guha Mazumder · 发表于：Journal of Toxicology Clinical Toxicology · 年份：2000 · DOI：10.1081/clt-100100949 · 被引用次数：180 · 研究领域：Arsenic contamination and mitigation、Aluminum toxicity and tolerance in plants and animals、Heavy Metal Exposure and Toxicity

OBJECTIVE: Noncirrhotic fibrosis of the liver is common in subjects chronically consuming ground water geologically contaminated with arsenic, but the mechanism of the hepatic fibrosis is not known. Because lipid peroxidation has been implicated in the development of several other forms of hepatic fibrosis, including iron and copper overload, we have explored the roles of oxidative stress and lipid peroxidation in the causation of hepatic fibrosis in a murine model of chronic arsenic toxicity. METHODS: Male BALB/c mice were given drinking water contaminated with arsenic (3.2 mg/L) or arsenic-free (<0.01 mg/L, control) ad libitum. Mice were sacrificed at 3, 6, 9, 12, and 15 months for examination of hepatic histology and assays of hepatic reduced glutathione content, lipid peroxidation, enzymes of the antioxidant defense system, and membrane-bound sodium/potassium ATPase (Na+/K+ ATPase). RESULTS: After 12 months of arsenic feeding, the liver weights increased significantly as did serum aspartate aminotransferase and alanine aminotransferase. After 6 months of arsenic feeding, hepatic glutathione and the enzymes glucose-6-phosphate dehydrogenase and glutathione peroxidase were significantly lower than those of the control group. Hepatic catalase activity was significantly reduced at 9 months in the arsenic-fed group, while glutathione-S-transferase and glutathione reductase activities were also significantly reduced at 12 and 15 months. Plasma membrane Na+/K+ ATPase activity wa...